ONCOBREAST-TEST Is a Quick Diagnostic, Prognostic and Predictive Method of Response to Systemic Treatment.

ONCOBREAST-TEST is a diagnostic and therapeutic procedure that is part of the comprehensive care of a patient with breast cancer.: Chemosensitivity of cancer cells was assessed using the MTT test, morphological assessment of cells, LDH activity in the culture medium, and flow cytometry technique (apoptosis, proliferation, CD24, CD44, GATA3, cytokeratin, Ki-67). Diagnostic tools included panels of simple tests which could be used to accurately predict the chemosensitivity of tumor cells previously isolated from a patient, even before actual chemotherapy. The proposed procedure allows for a simple (based on MTT results, cell morphology, LDH concentration), minimally invasive, quick, and accurate assessment of the sensitivity of breast cancer cells to the drugs used and, to select the most effective treatment plan as part of personalized therapy. In a patient with NOS G3, the most promising therapy will be docetaxel with cyclophosphamide and in the case of a patient with NOS G1, paclitaxel alone and in combination with trastuzumab. The implementation of such a procedure would undoubtedly increase the effectiveness of chemotherapy, reduce side effects by excluding drugs that are ineffective before using them, protect the patient's health, and shorten the treatment time, bringing economic and social benefits.

Fluorescent Polymers Conspectus.

The development of luminescent materials is critical to humankind. The Nobel Prizes awarded in 2008 and 2010 for research on the development of green fluorescent proteins and super-resolved fluorescence imaging are proof of this (2014). Fluorescent probes, smart polymer machines, fluorescent chemosensors, fluorescence molecular thermometers, fluorescent imaging, drug delivery carriers, and other applications make fluorescent polymers (FPs) exciting materials. Two major branches can be distinguished in the field: (1) macromolecules with fluorophores in their structure and (2) aggregation-induced emission (AIE) FPs. In the first, the polymer (which may be conjugated) contains a fluorophore, conferring photoluminescent properties to the final material, offering tunable structures, robust mechanical properties, and low detection limits in sensing applications when compared to small-molecule or inorganic luminescent materials. In the latter, AIE FPs use a novel mode of fluorescence dependent on the aggregation state. AIE FP intra- and intermolecular interactions confer synergistic effects, improving their properties and performance over small molecules aggregation-induced, emission-based fluorescent materials (AIEgens). Despite their outstanding advantages (over classic polymers) of high emission efficiency, signal amplification, good processability, and multiple functionalization, AIE polymers have received less attention. This review examines some of the most significant advances in the broad field of FPs over the last six years, concluding with a general outlook and discussion of future challenges to promote advancements in these promising materials that can serve as a springboard for future innovation in the field.

Diagnosis of Fetal Alcohol Spectrum Disorders (FASDs): Guidelines of Interdisciplinary Group of Polish Professionals.

(1) Background: Considerable prevalence in Poland and serious health consequences of prenatal alcohol exposure indicated the need to develop national guidelines for the diagnosis of fetal alcohol spectrum disorders (FASDs). It was assumed that the guidelines must be in line with international standards but adjusted to the Polish context. (2) Methods: Work on recommendations was carried out by an interdisciplinary team of Polish specialists. Its first stage was to assess the usefulness in our country of the U.S. and Canadian guidelines. In the second stage, after several rounds of discussions, a consensus was achieved. (3) Results: The Polish guidelines for diagnosing FASD cover the following issues: 1. distinguished diagnostic categories; 2. diagnostic procedure; 3. assessment of prenatal exposure to alcohol; 4. assessment of sentinel facial dysmorphias; 5. assessment of body weight, height, and head circumference; 6. neurodevelopmental assessment. An important element of the recommendation is appendices containing practical tools that are useful in the diagnostic procedure. (4) Conclusions: National guidelines may improve the quality and standardization of FASD diagnosis in Poland, but their practical utility has to be monitored.

Mixed-Charge Nanocarriers Allow for Selective Targeting of Mitochondria by Otherwise Nonselective Dyes.

Targeted delivery of molecular cargos to specific organelles is of paramount importance for developing precise and effective therapeutics and imaging probes. This work describes a disulfide-based delivery method in which mixed-charged nanoparticles traveling through the endolysosomal tract deliver noncovalently bound dye molecules selectively into mitochondria. This system comprises three elements: (1) The nanoparticles deliver their payloads by a kiss-and-go mechanism - that is, they drop off their dye cargos proximate to mitochondria but do not localize therein; (2) the dye molecules are by themselves nonspecific to any cellular structures but become so with the help of mixed-charge nanocarriers; and (3) the dye is engineered in such a way as to remain in mitochondria for a long time, up to days, allowing for observing dynamic remodeling of mitochondrial networks and long-term tracking of mitochondria even in dividing cells. The selectivity of delivery and long-lasting staining derive from the ability to engineer charge-imbalanced, mixed [+/-] on-particle monolayers and from the structural features of the cargo. Regarding the former, the balance of [+] and [-] ligands can be adjusted to limit cytotoxicity and control the number of dye molecules adsorbed onto the particles' surfaces. Regarding the latter, comparative studies with multiple dye derivatives we synthesized rationalize the importance of polar groups, long alkyl chains, and disulfide moieties in the assembly of fluorescent nanoconstructs and long-lasting staining of mitochondria. Overall, this strategy could be useful for delivering hydrophilic and/or anionic small-molecule drugs difficult to target to mitochondria by classical approaches.

Characteristics and outcomes of in-hospital cardiac arrest in COVID-19. A systematic review and meta-analysis.

BACKGROUND: The purpose herein, was to perform a systematic review of interventional outcome studies in patients with in-hospital cardiac arrest before and during the coronavirus disease 2019 (COVID-19) pandemic period. METHODS: A meta-analysis was performed of publications meeting the following PICOS criteria: (1) participants, patients > 18 years of age with cardiac arrest due to any causes; (2) intervention, cardiac arrest in COVID-19 period; (3) comparison, cardiac arrest in pre-COVID-19 period; (4) outcomes, detailed information for survival; (5) study design, randomized controlled trials, quasi-randomized or observational studies comparing cardiac arrest in COVID-19 and pre-COVID-19 period for their effects in patients with cardiac arrest. RESULTS: Survival to hospital discharge for the pre-pandemic and pandemic period was reported in 3 studies (n =1432 patients) and was similar in the pre-pandemic vs. the pandemic period, 35.6% vs. 32.1%, respectively (odds ratio [OR] 1.72; 95% confidence interval [CI] 0.81-3.65; p = 0.16; I2 = 72%). Return of spontaneous circulation was reported by all 4 studies and were also similar in the pre and during COVID-19 periods, 51.9% vs. 48.7% (OR 1.27; 95% CI 0.78-2.07; p = 0.33; I2 = 71%), respectively. Pooled analysis of cardiac arrest recurrence was also similar, 24.9% and 17.9% (OR 1.60; 95% CI 0.99-2.57; p = 0.06; I2 = 32%) in the pre and during COVID-19 cohorts. Survival with Cerebral Performance Category 1 or 2 was higher in pre vs. during pandemic groups (27.3 vs. 9.1%; OR 3.75; 95% CI 1.26-11.20; p = 0.02). Finally, overall mortality was similar in the pre vs. pandemic groups, 65.9% and 67.2%, respectively (OR 0.67; 95% CI 0.33-1.34; p = 0.25; I2 = 76%). CONCLUSIONS: Compared to the pre-pandemic period, in hospital cardiac arrest in COVID-19 patients was numerically higher but had statistically similar outcomes.

Impact of Coronavirus Disease 2019 on Out-of-Hospital Cardiac Arrest Survival Rate: A Systematic Review with Meta-Analysis.

Out-of-hospital cardiac arrest (OHCA) is a challenge for medical staff, especially in the COVID-19 period. The COVID-19 disease caused by the SARS-CoV-2 coronavirus is highly infectious, thus requiring additional measures during cardiopulmonary resuscitation (CPR). Since CPR is a highly aerosol-generating procedure, it carries a substantial risk of viral transmission. We hypothesized that patients with diagnosed or suspected COVID-19 might have worse outcomes following OHCA outcomes compared to non-COVID-19 patients. To raise awareness of this potential problem, we performed a systematic review and meta-analysis of studies that reported OHCA in the pandemic period, comparing COVID-19 suspected or diagnosed patients vs. COVID-19 not suspected or diagnosed group. The primary outcome was survival to hospital discharge (SHD). Secondary outcomes were the return of spontaneous circulation (ROSC), survival to hospital admission or survival with favorable neurological outcomes. Data including 4210 patients included in five studies were analyzed. SHD in COVID-19 and non-COVID-19 patients were 0.5% and 2.6%, respectively (odds ratio, OR = 0.25; 95% confidence interval, CI: 0.12, 0.53; p < 0.001). Bystander CPR rate was comparable in the COVID-19 vs. not COVID-19 group (OR = 0.88; 95% CI: 0.63, 1.22; p = 0.43). Shockable rhythms were observed in 5.7% in COVID-19 patients compared with 37.4% in the non-COVID-19 group (OR = 0.19; 95% CI: 0.04, 0.96; p = 0.04; I2 = 95%). ROSC in the COVID-19 and non-COVID-19 patients were 13.3% vs. 26.5%, respectively (OR = 0.67; 95% CI: 0.55, 0.81; p < 0.001). SHD with favorable neurological outcome was observed in 0% in COVID-19 vs. 3.1% in non-COVID-19 patients (OR = 1.35; 95% CI: 0.07, 26.19; p = 0.84). Our meta-analysis suggests that suspected or diagnosed COVID-19 reduces the SHD rate after OHCA, which seems to be due to the lower rate of shockable rhythms in COVID-19 patients, but not due to reluctance to bystander CPR. Future trials are needed to confirm these preliminary results and determine the optimal procedures to increase survival after OHCA in COVID-19 patients.

Out-of-hospital cardiac arrest treated by emergency medical service teams during COVID-19 pandemic: A retrospective cohort study.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a challenge for medical personnel, especially in the current COVID-19 pandemic, where medical personnel should perform resuscitation wearing full personal protective equipment. This study aims were to assess the characteristics and outcomes of adults who suffered an OHCA in the COVID-19 pandemic treated by emergency medical service (EMS) teams. METHODS: All EMS-attended OHCA adults over than 18 years in the Polish EMS registry were analyzed. The retrospective EMS database was conducted. EMS interventions performed between March 1, and April 30, 2020 were retrospectively screened. RESULTS: In the study period EMS operated 527 times for OHCA cases. The average age of patients with OHCA was 67.8 years. Statistically significantly more frequently men were involved (64.3%). 298 (56.6%) of all OHCA patients had resuscitation attempted by EMS providers. Among resuscitated patients, 73.8% were cardiac etiology. 9.4% of patients had return of spontaneous circulation, 27.2% of patients were admitted to hospital with ongoing chest compression. In the case of 63.4% cardiopulmonary resuscitation was ineffective and death was determined. CONCLUSIONS: The present study found that OHCA incidence rate in the Masovian population (central region of Poland) in March-April 2020 period was 12.2/100,000 adult inhabitants. Return of spontaneous circulation in EMS was observed only in 9.4% of resuscitated patients. The presence of shockable rhythms was associated with better prognosis. The prehospital mortality, even though it was high, did not differ from those reported by other studies.

Targeted crystallization of mixed-charge nanoparticles in lysosomes induces selective death of cancer cells.

Lysosomes have become an important target for anticancer therapeutics because lysosomal cell death bypasses the classical caspase-dependent apoptosis pathway, enabling the targeting of apoptosis- and drug-resistant cancers. However, only a few small molecules-mostly repurposed drugs-have been tested so far, and these typically exhibit low cancer selectivity, making them suitable only for combination therapies. Here, we show that mixed-charge nanoparticles covered with certain ratios of positively and negatively charged ligands can selectively target lysosomes in cancerous cells while exhibiting only marginal cytotoxicity towards normal cells. This selectivity results from distinct pH-dependent aggregation events, starting from the formation of small, endocytosis-prone clusters at cell surfaces and ending with the formation of large and well-ordered nanoparticle assemblies and crystals inside cancer lysosomes. These assemblies cannot be cleared by exocytosis and cause lysosome swelling, which gradually disrupts the integrity of lysosomal membranes, ultimately impairing lysosomal functions and triggering cell death.

Elevated serum concentrations of IGF-1 and IGF-1R in patients with thyroid cancers.

BACKGROUND: The rising incidence of thyroid cancer observed in the last few decades requires an improvement in diagnostic tools and management techniques for patients with thyroid nodules. AIMS: The aim of this study was to assess serum concentrations of IGF-1 and IGF-1R in patients diagnosed with thyroid cancers. METHODS: 36 patients diagnosed with papillary thyroid cancer (PTC), 11 subjects with follicular thyroid cancer (FTC), 9 patients with anaplastic thyroid cancer (ATC) and 19 subjects with multinodular nontoxic goiter (MNG) were enrolled to the study. The control group (CG) consisted of 20 healthy volunteers. Blood samples were collected one day before surgery. Serum IGF-1 and IGF-1R concentrations were measured using specific ELISA methods. RESULTS: Significantly higher concentrations of IGF-1 were found in patients with PTC as compared with controls but not that obtained from subjects diagnosed with MNG. The concentration of IGF-1R was significantly elevated in subjects with PTC and ATC as compared with healthy volunteers. Similarly, patients diagnosed with PTC or ATC presented significantly higher serum concentration of IGF-1R in comparison to the MNG group. CONCLUSIONS: Our results show that the IGF-1 - IGF-1R axis plays a significant role in the development of PTC and ATC and imply that serum concentrations of both cytokines may be considered as additional markers for the differentiation of malignancies during the preoperative diagnosis of patients with thyroid gland tumors. These results indicate that IGF-1R serum concentrations allow us to differentiate between MNG and PTC or ATC. Moreover IGF-1R serum values appear to be better predictor of PTC and ATC than IGF-1 concentrations.

Dysregulation in IGF-1R, FGFR4 and ßKlotho signaling in patients with medullary thyroid cancer.

BACKGROUND: Medullary thyroid cancer (MTC) is a relatively rare thyroid neoplasm derived from neuroendocrine C cells which secrete calcitonin. αKlotho (αKL) and ßKlotho (ßKL) are transmembrane proteins which modulate different signaling systems, such as endocrine FGFs and IGF1 pathways. Dysregulation of the FGF19/FGFR4/ßKL and IGF-1/IGF-1R/αKL signaling axes has been implicated in the pathogenesis of several cancers. However, their role in the pathogenesis of MTC has not been determined. METHODS: The aim of this study was to assess αKL, ßKL, FGF19, IGF-1, FGFR4, and IGF-1R concentrations in a group of 11 patients with medullary thyroid cancer (MTC). The control group consisted of 20 healthy volunteers. Serum concentrations of these factors were measured using specific ELISA methods. RESULTS: Significantly lower concentrations of ßKL and higher concentrations of FGFR4 and IGF-1R were found in patients with MTC as compared to controls. CONCLUSIONS: Our results indicate that a disrupted signaling pathway for ßKL, FGFR4 and IGF-1R may play a role in the development of medullary thyroid cancers. However, further studies are required to confirm these findings and to use this knowledge in clinical practice.

Expression of α-Klotho protein in human thyroid cancers - an immunohistochemical study.

INTRODUCTION: The α-Klotho protein was discovered as a gene controlling the process of aging, but further studies indicated that it also plays the role of a tumour suppressor. Although numerous studies were performed on the role of the α-Klotho gene and protein in neoplasia, the data on α-Klotho protein expression in thyroid cancers are very scarce. Our study presents the immunohistochemical investigation of α-Klotho expression in benign and malignant thyroid tumours. MATERIAL AND METHODS: The material included samples of benign (nodular hyperplasia, follicular adenoma), differentiated (follicular and papillary) cancers and aggressive thyroid cancers of low differentiation grade. The samples were immunostained using two different monoclonal anti-α-Klotho antibodies. RESULTS: From the two antibodies used in this study, one (EPR6856) reacted probably with the soluble form of Klotho and immunostained mostly the colloid filling thyroid follicles and intravascular or extravascular serum deposits. The other (A-9 antibody) immunostained the follicular epithelium in benign thyroid lesions as well as the epithelial tumoural cells in differentiated thyroid (follicular and papillary cancers). In the thyroid cancers of high malignancy, the immunostaining with A-9 anti-α-Klotho antibody was (except in one case) negative or very weak. CONCLUSION: Our results indicate that lowered expression of a- Klotho is involved in the process of thyroid neoplasia.

Alteration in the serum concentrations of FGF19, FGFR4 and ßKlotho in patients with thyroid cancer.

INTRODUCTION: ßKlotho (ßKL) is known to act as co-receptor for fibroblast growth factor receptor 4 (FGFR4) which is the main cognate receptor for fibroblast growth factor 19 (FGF19). Dysregulation of this FGF19/FGFR4/ßKL signaling axis has been implicated in the pathogenesis of several cancers. However, its role in the pathogenesis of thyroid cancer has not been determined. MATERIALS AND METHODS: The aim of this study was to assess FGF19, FGFR4 and ßKL concentrations in a group of 36 patients with papillary thyroid cancer (PTC), 11 patients with follicular thyroid cancer (FTC), 9 patients with anaplastic thyroid cancer (ATC) and a group of 19 subjects with multinodular nontoxic goiter (MNG). The control group consisted of 20 healthy volunteers. Serum FGF19, FGFR4 and ßKL concentrations were measured using specific ELISA methods. RESULTS: Significantly lower concentrations of ßKL and higher concentrations of FGF19 were found in patients with PTC, FTC and ATC as compared with MNG group and controls. An elevation of FGFR4 serum concentration was observed in all thyroid cancer groups in comparison to MNG group and controls; however, in FTC group it was statistically insignificant. A positive correlation was found between ßKL and FGFR4 concentrations in PTC patients. The levels of ßKL, FGF19 and FGFR4 did not differ significantly between MNG group and healthy controls. CONCLUSIONS: Our results indicate that a disrupted FGF19/FGFR4/ßKL signaling pathway may play a role in the development of thyroid cancers. However, further studies are needed to elucidate the molecular mechanism of the neoplastic transition of thyroid epithelial cells.

FASD Prevalence among Schoolchildren in Poland.

BACKGROUND: Prenatal Alcohol Exposure is a major cause of brain damage and developmental delay, known as Fetal Alcohol Spectrum Disorders (FASD) but in Poland is rarely diagnosed and the scale of problem is not known. METHODS: An active case ascertainment approach was applied to estimate the prevalence of FASD among 7-9 years olds. Pre-screening was conducted in 113 randomly selected regular and special schools. In the screening phase participated 280 children (54% from the risk group, 60% boys). The entire number of eligible students (N = 2500) was taken as a denominator. RESULTS: The prevalence of FASD is not lower than 2%, including 0.4% of Fetal Alcohol Syndrome. CONCLUSIONS: Neurodevelopmental disorders associated with PAE are a serious challenge for the public health system. Development of procedures and services to diagnose and to support individuals affected by PAE and their families is an urgent need in Poland.

Engineering Gram Selectivity of Mixed-Charge Gold Nanoparticles by Tuning the Balance of Surface Charges.

Nanoparticles covered with ligand shells comprising both positively and negatively charged ligands exhibit Gram-selective antibacterial action controlled by a single experimental parameter, namely the proportion of [+] and [-] ligands tethered onto these particles. Gram selectivity is attributed to the interplay between polyvalent electrostatic and non-covalent interactions that work in unison to disrupt the bacterial cell wall. The [+/-] nanoparticles are effective in low doses, are non-toxic to mammalian cells, and are tolerated well in mice. These results constitute the first example of rational engineering of Gram selectivity at the (macro)molecular level.

Cationization versus surface activity--the effect on electrospray ionization.

Ethoxylated fatty alcohols, C(12)E(1), C(12)E(2), C(18)E(1) and C(18)E(2), were studied by electrospray ionization mass spectrometry (E is the ethoxylene unit OCH(2)CH(2)). For compounds containing two ethoxylene units, which form quite stable adducts with sodium cation, the abundances of [M + Na](+) ions were not affected by alkyl chain, so the hydrophobic effect was not observed. For the compounds containing one ethoxylene unit, forming rather unstable adducts with sodium, the hydrophobic effect was clearly seen since the [C(18)E(1) + Na](+) ion was more abundant than the [C(12)E(1) + Na](+) ion. Two ethoxylene units are not able to form stable adducts with potassium cations, therefore the hydrophobic effect was observed for the [C(12)E(2) + K](+) and [C(18)E(2) + Na](+) ions, the latter being more abundant than the former. For lithium cation adducts with C(12)E(1) and C(18)E(1), the hydrophobic effect was observed, but was less manifested than for sodium cations since lithium adducts are more stable than sodium ones. C(18)E(1) and C(18)E(2) gave more intense signals at higher cone voltage values than C(12)E(1) and C(12)E(2), respectively. However, this is not related to the hydrophobic effect but to the collisions being less effective for the former.